It arises from a nucleus situated in the floor of the cerebral aqueduct, opposite the upper part of the inferior colliculus. From its origin it runs downward through the tegmentum, and then turns backward into the upper part of the anterior medullary velum. Here it decussates with its fellow of the opposite side and emerges from the surface of the velum at the side of the frenulum veli, immediately behind the inferior colliculus.

The nerve is directed across the superior cerebellar peduncle, and then winds forward around the cerebral peduncle, immediately above the pons, pierces the dura mater in the free border of the tentorium cerebelli, just behind, and lateral to, the posterior clinoid process, and passes forward in the lateral wall of the cavernous sinus, between the oculomotor nerve and the ophthalmic division of the trigeminal. It crosses the oculomotor nerve, and enters the orbit through the superior orbital fissure. It now becomes the highest of all the nerves, and lies medial to the frontal nerve. In the orbit it passes medialward, above the origin of the Levator palpebræ superioris, and finally enters the orbital surface of the Obliquus superior.

In the lateral wall of the cavernous sinus the trochlear nerve forms communications with the ophthalmic division of the trigeminal and with the cavernous plexus of the sympathetic. In the superior orbital fissure it occasionally gives off a branch to the lacrimal nerve. It gives off a recurrent branch which passes backward between the layers of the tentorium cerebelli and divides into two or three filaments which may be traced as far as the wall of the transverse sinus.